Shyam Kishor Sah1, Kyung Ho Park2, Chae-Ok Yun3, Kyung-Sun Kang4, Tae-Yoon Kim1. 1. 1 Laboratory of Dermato-Immunology, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea. 2. 2 Biological Sciences Center, University of Minnesota Twin Cities , St. Paul, Minnesota. 3. 3 Department of Bioengineering, College of Engineering, Hanyang University , Seoul, Republic of Korea. 4. 4 Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University , Seoul, Republic of Korea.
Abstract
AIMS: The immunomodulatory and anti-inflammatory properties of mesenchymal stem cells (MSCs) have been proposed in several autoimmune diseases and successfully tested in animal models, but their contribution to psoriasis and underlying pathways remains elusive. Likewise, an increased or prolonged presence of reactive oxygen species and aberrant antioxidant systems in skin are known to contribute to the development of psoriasis and therefore effective antioxidant therapy is highly required. We explored the feasibility of using extracellular superoxide dismutase (SOD3)-transduced allogeneic MSCs as a novel therapeutic approach in a mouse model of imiquimod (IMQ)-induced psoriasis-like inflammation and investigated the poorly understood underlying mechanism. In addition, the chronicity and late-phase response of inflammation were evaluated during continued activation of antigen receptors by applying a booster dose of IMQ. RESULTS: Subcutaneous injection of allogeneic SOD3-transduced MSCs significantly prevented psoriasis development in our IMQ-induced mouse model, likely through a suppression of proliferation and infiltration of various effector cells into skin with a concomitant modulated cytokine and chemokine expression and inhibition of signaling pathways such as toll-like receptor-7, nuclear factor-kappa B, p38 mitogen-activated kinase, and Janus kinase-signal transducer and activator of transcription, as well as adenosine receptor activation. INNOVATION AND CONCLUSION: Our data offer a novel therapeutic approach to chronic inflammatory skin diseases such as psoriasis by leveraging immunomodulatory effects of MSCs as well as SOD3 expression.
AIMS: The immunomodulatory and anti-inflammatory properties of mesenchymal stem cells (MSCs) have been proposed in several autoimmune diseases and successfully tested in animal models, but their contribution to psoriasis and underlying pathways remains elusive. Likewise, an increased or prolonged presence of reactive oxygen species and aberrant antioxidant systems in skin are known to contribute to the development of psoriasis and therefore effective antioxidant therapy is highly required. We explored the feasibility of using extracellular superoxide dismutase (SOD3)-transduced allogeneic MSCs as a novel therapeutic approach in a mouse model of imiquimod (IMQ)-induced psoriasis-like inflammation and investigated the poorly understood underlying mechanism. In addition, the chronicity and late-phase response of inflammation were evaluated during continued activation of antigen receptors by applying a booster dose of IMQ. RESULTS: Subcutaneous injection of allogeneic SOD3-transduced MSCs significantly prevented psoriasis development in our IMQ-induced mouse model, likely through a suppression of proliferation and infiltration of various effector cells into skin with a concomitant modulated cytokine and chemokine expression and inhibition of signaling pathways such as toll-like receptor-7, nuclear factor-kappa B, p38 mitogen-activated kinase, and Janus kinase-signal transducer and activator of transcription, as well as adenosine receptor activation. INNOVATION AND CONCLUSION: Our data offer a novel therapeutic approach to chronic inflammatory skin diseases such as psoriasis by leveraging immunomodulatory effects of MSCs as well as SOD3 expression.
Authors: Luciano C Amado; Anastasios P Saliaris; Karl H Schuleri; Marcus St John; Jin-Sheng Xie; Stephen Cattaneo; Daniel J Durand; Torin Fitton; Jin Qiang Kuang; Garrick Stewart; Stephanie Lehrke; William W Baumgartner; Bradley J Martin; Alan W Heldman; Joshua M Hare Journal: Proc Natl Acad Sci U S A Date: 2005-08-01 Impact factor: 11.205
Authors: Leslie van der Fits; Sabine Mourits; Jane S A Voerman; Marius Kant; Louis Boon; Jon D Laman; Ferry Cornelissen; Anne-Marie Mus; Edwin Florencia; Errol P Prens; Erik Lubberts Journal: J Immunol Date: 2009-05-01 Impact factor: 5.422
Authors: Luis A Ortiz; Maria Dutreil; Cheryl Fattman; Amitabh C Pandey; German Torres; Kristina Go; Donald G Phinney Journal: Proc Natl Acad Sci U S A Date: 2007-06-14 Impact factor: 11.205
Authors: Kerstin Wolk; Harald S Haugen; Wenfeng Xu; Ellen Witte; Kim Waggie; Monica Anderson; Elmar Vom Baur; Katrin Witte; Katarzyna Warszawska; Sandra Philipp; Caroline Johnson-Leger; Hans-Dieter Volk; Wolfram Sterry; Robert Sabat Journal: J Mol Med (Berl) Date: 2009-03-30 Impact factor: 4.599
Authors: Joji Kusuyama; Ana Barbara Alves-Wagner; Royce H Conlin; Nathan S Makarewicz; Brent G Albertson; Noah B Prince; Shio Kobayashi; Chisayo Kozuka; Magnus Møller; Mette Bjerre; Jens Fuglsang; Emily Miele; Roeland J W Middelbeek; Yang Xiudong; Yang Xia; Léa Garneau; Jayonta Bhattacharjee; Céline Aguer; Mary Elizabeth Patti; Michael F Hirshman; Niels Jessen; Toshihisa Hatta; Per Glud Ovesen; Kristi B Adamo; Eva Nozik-Grayck; Laurie J Goodyear Journal: Cell Metab Date: 2021-03-25 Impact factor: 27.287